27 articles - From Saturday Jan 15 2022 to Friday Jan 21 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Blood |
A Congenital Anemia Reveals Distinct Targeting Mechanisms for Master Transcription Factor GATA1. Through integrative functional approaches, we demonstrate that these mutations perturb GATA1 transcriptional activity by partially impairing nuclear localization and selectively altering precise chromatin occupancy by GATA1. These alterations in chromatin occupancy and concordant chromatin accessibility changes alter faithful gene expression, with failure to both effectively silence and activate select genes necessary for effective terminal red cell production. We demonstrate how disease-causing mutations can reveal regulatory mechanisms that enable the faithful genomic targeting of master TFs during cellular differentiation. |
Formation of neutrophil extracellular traps requires actin cytoskeleton rearrangements. Neutrophils from patients with very rare inherited actin polymerization defects by either ARPC1B- or MKL1-deficiency also failed to show NETosis. We found that upon inhibition of actin dynamics there is a lack of translocation of NE to the nucleus, which may well explain the impaired NET formation. Collectively, our data illustrate the essential requirement of an intact and active actin polymerization process, as well as active myosin II to enable the release of nuclear DNA by neutrophils during NET formation. |
HMGB1-Mediated Restriction of EPO Signaling Contributes to Anemia of Inflammation. Furthermore, surface plasmon resonance studies highlight the ability of HMGB1 to interfere with the binding between EPO and the EPOR. Administration of a monoclonal anti-HMGB1 antibody after sepsis onset in mice partially restores EPO signaling in vivo. Thus, HMGB1-mediated restriction of EPO signaling contributes to the chronic phase of anemia of inflammation. |
Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. The responses seen in patients with KHE with KMP were profound and encouraging, suggesting that sirolimus plus prednisolone should be considered a valid treatment for KHE with KMP. ClinicalTrial. gov, number NCT03188068. |
| Blood Adv |
Distinct clinical and genetic features of hepatitis B virus-associated follicular lymphoma in Chinese patients. Finally, we identified an increased infiltration of CD8+ memory T-cells, CD4+ Th1-cells, and M1-macrophages and higher T-cell exhaustion gene signature in HBsAg+ FL samples. Taken together, we present new genetic/epigenetic evidence that links chronic HBV infection to B-cell lymphomagenesis, and HBV-associated FL is likely to have a distinct cell-of-origin and represent as a separate subtype of FL. Targetable genetic/epigenetic alterations identified in tumors and their associated tumor microenvironment may provide potential novel therapeutic approaches for this subgroup of patients. |
Indirect Comparison of Tisagenlecleucel and Historical Treatments for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Median OS was 12.48 months (JULIET) vs 4.34-4.40 months (CORAL) for the FAS, and 8.25 (JULIET) vs 4.04-4.86 (CORAL) for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared to historical treatments among the FAS (adjusted response rate difference [95% CI], both FSW and SMRW: 36% [22%, 0.48%]; p<0.001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; p=0.043). This analysis supports that improved response and OS are achieved in r/r DLBCL patients treated with tisagenlecleucel when compared to those treated with alternative historical treatments. |
Regenerating Islet-Derived 3-alpha is a Prognostic Biomarker for Gastrointestinal Chronic Graft-Versus-Host Disease. In multivariate Cox regression model, patients with high Reg3a were 1.9 times more likely to die without relapse. Our findings demonstrate the utility of Reg3a as a prognostic marker for GI-cGVHD. These data warrant prospective biomarker validation studies. |
Single-cell analysis reveals selection of TP53-mutated clones after MDM2 inhibition. At the single cell level the presence of additional mutations does not influence the selection of TP53 mutant cells by MDM2 inhibitor treatment. Also, we describe an in vitro test allowing to predict the emergence of TP53 mutated clones. Altogether, this is the first demonstration that a drug treatment can directly favor the emergence of TP53-mutated subclones in MPN. |
Triple combination of BET plus PI3K and NF- The triple combination also enhanced apoptosis induction by elevating the expression of active caspase-3 and cleaved PARP. Importantly, the triple combination prolonged the survival of ATL-bearing xenograft mice and inhibited the proliferation of ATL cells from PBMCs of both acute and smoldering/chronic ATL patients. Therefore, our data provide the rationale for a clinical trial exploring the multi-agent combination of BET, PI3K/AKT, and NF- |
| Blood Cancer J |
European LeukemiaNet-defined primary refractory acute myeloid leukemia: the value of allogeneic hematopoietic stem cell transplant and overall response. 1/2/5-year overall survival (OS) rates were 63%/38%/33% in patients who received AHSCT (n |
| Lancet Haematol |
Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). Interpretation Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Funding Oncopeptides AB. |
| Leukemia |
CD19/BAFF-R dual-targeted CAR T cells for the treatment of mixed antigen-negative variants of acute lymphoblastic leukemia. Immunodeficient mice engrafted with mixed CD19-/- and BAFF-R-/- variant ALL cells and treated with a single dose of CD19/BAFF-R dual CAR T cells experienced complete eradication of both CD19-/- and BAFF-R-/- ALL variants, whereas mice treated with monospecific CD19 or BAFF-R CAR T cells succumbed to outgrowths of CD19-/BAFF-R+ or CD19+/BAFF-R- tumors, respectively. Further, CD19/BAFF-R dual CAR T cells showed prolonged in vivo persistence, raising the possibility that these cells may have the potential to promote durable remissions. Together, our data support clinical translation of BAFF-R/CD19 dual CAR T cells to treat ALL. |
Cell-free DNA for the detection of emerging treatment failure in relapsed/ refractory multiple myeloma. Multivariate hazard modelling confirmed cfDNA as independent risk factor (HR 96.6, P |
HMCES safeguards genome integrity and long-term self-renewal of hematopoietic stem cells during stress responses. Moreover, Hmces-deficient mice died from bone marrow failure after exposure to sublethal irradiation, which also produces ROS. Notably, dysregulation of HMCES occurs frequently in acute lymphocytic leukemia (ALL) and is associated with poor clinical outcomes. Together, our findings not only highlighted HMCES as a novel genome protector in activated HSCs, but also position it as a potential selective target against ALL while sparing normal hematopoiesis. |
Inhibition of the deubiquitinating enzyme USP47 as a novel targeted therapy for hematologic malignancies expressing mutant EZH2. Inhibition of USP47 would be anticipated to block the function of mutated EZH2 through induction of EZH2 degradation by promoting its ubiquitination. Moreover, targeting of USP47 leads to death of mutant EZH2-positive cells in vitro and in vivo. Taken together, we propose targeting USP47 with a small molecule inhibitor as a novel potential therapy for DLBCL and other hematologic malignancies characterized by mutant EZH2 expression. |
Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL. Functional analysis by BH3-profiling and analysis of protein complexes revealed that venetoclax-treated ALL cells are dependent on MCL-1 and BCL-XL, indicating that MCL-1 or BCL-XL provide an Achilles heel in BCL-2-inhibited cells. The effect of combining BCL-2 and MCL-1 inhibition by venetoclax and S63845 was evaluated in vivo and strongly enhanced anti-leukemia activity was found in a pre-clinical patient-derived xenograft model. Our study offers in-depth molecular analysis of mutual substitution of BCL-2 family proteins in acute lymphoblastic leukemia and provides targets for combination treatment in vivo and in ongoing clinical studies. |
| Thromb Haemost |
Incidence and Outcomes Associated with 6841 Isolated Distal Deep Vein Thromboses in Patients with 13 Common Cancers. iDDVT represented 11% of CAT. The risk of rVTE after iDDVT was similar to other sites of CAT and rVTE occurred in more proximal locations after an incident iDDVT. IDDVT was associated with increased mortality and this effect was similar to that of PE or pDVT for most cancer types. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
| J Hematol Oncol |
Immune checkpoint-targeted antibodies: a room for dose and schedule optimization? Dosing and scheduling of these biologics were established according to conventional drug development models, even though the determination of a maximum tolerated dose in the clinic could only be defined for anti-CTLA-4. Given the pharmacology of these monoclonal antibodies, their high interpatient pharmacokinetic variability, the actual clinical benefit as monotherapy that is observed only in a specific subset of patients, and the substantial cost of these treatments, a number of questions arise regarding the selected dose and the dosing interval. This review aims to outline the development of these immunotherapies and considers optimization options that could be used in clinical practice. |
| Thromb Haemost |
Letters to the editors and authors’ replies
| Am J Hematol |
| Leukemia |
all remaining publications eg case reports, images of the month, etc…
| Lancet Haematol |
| Leukemia |